Expression And Significance Of NLRP3 Inflammasome In Patients With Inflammatory Bowel Disease

BackgroundInflammatory bowel disease(IBD) is a kind of disease characterized by chronic and relapsing inflammation of the gastrointestinal tract. Ulcerative colitis(UC) and Crohn's disease(CD) are the two main forms of inflammatory bowel disease. IBD affects millions of people around the world, the incidence of IBD has been rising not only in Western countries, but also in low-incidence areas such as Asia and developing countries. Currently, it is believed that the initiation and development of IBD are multifactors involving genetic, immunized, infectious and environmental factors and so on. Although the precise etiology of this disease is still not completely confirmed, accumulating evidence indicates that the activated mucosal immune system plays a key role for IBD. NLRP3 inflammasome,an intracellular receptor of innate immunity which can regulate inflammatory response, is a complex of a variety of proteins. It can promote the maturation and secretion of IL-1?(interleukin-1?) and IL-18 by adjusting the activity of Caspase-1 and thus participating in the regulation of the body's innate immune response. Recent studies indicate that NLRP3 inflammasome is an important component of the inflammatory process and its dysregulation contributes to IBD. ObjectiveThe study was designed to examine the expression of the NLRP3 inflammasome and its downstream inflammatory factor IL-1?in the intestine tissue of patients with inflammatory bowel disease, compare their differences and explore the significance of NLRP3 inflammasome in IBD pathogenesis. MethodsA total of 10 CD patients and 40 UC patients were chosen, among which, 20 patients were mild UC, and 20 patients were moderate to severe UC, the stump normal intestinal tissues from 20 cancer patients were collected as control group. The expression of NLRP3 and IL-1 ? in colonic tissue was detected by immunohistochemisty, and the expression of its mRNA in colonic tissue was identified by RT-qPCR technique. Results(1)The results of HE showed that compared with the stump normal intestinal tissues from colon cancer patients, the colonic mucosal layer of Crohn's disease patients, ulcerative colitis patients(mild, moderate to severe) was infiltrated with more lymphocytes and plasma cells, crypts can be even seen destroyed, and score of HI was higher than the control group.(2)The results of immunohistochemistry showed that although the NLRP3 and IL-1?can be detected in the stump normal intestinal tissues from colon cancer patients, the expression was at a low level. The staining intensity of NLRP3 and IL-1?in Crohn's disease patients and ulcerative colitis patients increased significantly.(3)The results of RT-qPCR showed that, the NLRP3 mRNA expression levels in intestinal tissue of Crohn's disease patients and ulcerative colitis patients were significantly higher than the stump normal intestinal tissues from colon cancer patients. And the difference was statistically significant(P <0.05). The IL-1?mRNA expression levels in intestinal tissue of Crohn's disease patients and ulcerative colitis patients were significantly higher than the stump normal intestinal tissues from colon cancer patients. And the difference was statistically significant(P <0.05).(4)The expression level of NLRP3 mRNA and the expression level of IL-1?mRNA in Crohn's disease was positively correlated(r=0.820,P < 0.01); The expression level of NLRP3 mRNA and the expression level of IL-1?mRNA in mild ulcerative colitis was positively correlated(r=0.696,P<0.01); The expression level of NLRP3 mRNA and the expression level of IL-1?mRNA in severe ulcerative colitis was positively correlated(r=0.783,P<0.01).ConclusionCrohn's disease and ulcerative colitis exhibited higher NLRP3 and IL-1?expression, and the two factors were positive correlation, this suggested that the NLRP3-IL-1? signaling pathway was involved in the pathogenesis of inflammatory bowel disease.